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Background: Older patients with metastatic castration-resistant prostate cancer (mCRPC) may be more prone to chemotherapy-induced hematological toxicity, but tailored docetaxel dosing guidelines in older patients are lacking because of conflicting data., Objective: This study aims to evaluate the impact of older age on the incidence of hematological toxicity in patients with mCRPC treated with docetaxel in daily clinical practice., Methods: This study included patients with mCRPC treated with docetaxel between January 2006 and January 2016 at the Netherlands Cancer Institute and Medical Center Slotervaart for whom dosing and hematological toxicity data were available from electronic patient records. We evaluated the impact of age on the incidence of grade 3 and 4 hematological toxicity., Results: In total, 175 patients treated with docetaxel were included in the analysis, with a median age of 67 years (range 47-86). Baseline hematological laboratory values were not age related. After the first treatment cycle, hematological toxicity occurred significantly more frequently in the oldest age quartile (25%, p = 0.02) than in the younger age quartiles (9%, 11%, and 7%, respectively, for age quartiles 1, 2, and 3)., Conclusion: The risk of hematological toxicity was significantly higher in the oldest age quartile than in younger patients with mCRPC treated with docetaxel in daily clinical practice.

The incidence of neutropenia in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel has been reported to be lower compared to patients with other solid tumors treated with a similar dose. It is suggested that this is due to increased clearance of docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid tumors by conducting a meta-analysis, (2) evaluate the incidence of neutropenia in patients with mCRPC vs other solid tumors in a clinical cohort, and (3) discuss potential clinical consequences. A meta-analysis was conducted of studies which reported areas under the plasma concentration-time curves (AUCs) of docetaxel and variability. In addition, grade 3/4 neutropenia was evaluated using logistic regression in a cohort of patients treated with docetaxel. The meta-analysis included 36 cohorts from 26 trials (n = 1150 patients), and showed that patients with mCRPC had a significantly lower mean AUC vs patients with other solid tumors (fold change [95% confidence interval (CI)]: 1.8 [1.5-2.2]), with corresponding AUCs of 1.82 and 3.30 mg∙h/L, respectively. Logistic regression, including 812 patient, demonstrated that patients with mCRPC had a 2.2-fold lower odds of developing grade 3/4 neutropenia compared to patients with other solid tumors (odds ratio [95%CI]: 0.46 [0.31-0.90]). These findings indicate that mCRPC patients have a lower risk of experiencing severe neutropenia, possibly attributable to lower systemic exposure to docetaxel., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The incidence of neutropenia in metastatic castration‐resistant prostate cancer (mCRPC) patients treated with docetaxel has been reported to be lower compared to patients with other solid tumors treated with a similar dose. It is suggested that this is due to increased clearance of docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid tumors by conducting a meta‐analysis, (2) evaluate the incidence of neutropenia in patients with mCRPC vs other solid tumors in a clinical cohort, and (3) discuss potential clinical consequences. A meta‐analysis was conducted of studies which reported areas under the plasma concentration‐time curves (AUCs) of docetaxel and variability. In addition, grade 3/4 neutropenia was evaluated using logistic regression in a cohort of patients treated with docetaxel. The meta‐analysis included 36 cohorts from 26 trials (n = 1150 patients), and showed that patients with mCRPC had a significantly lower mean AUC vs patients with other solid tumors (fold change [95% confidence interval (CI)]: 1.8 [1.5‐2.2]), with corresponding AUCs of 1.82 and 3.30 mg∙h/L, respectively. Logistic regression, including 812 patient, demonstrated that patients with mCRPC had a 2.2‐fold lower odds of developing grade 3/4 neutropenia compared to patients with other solid tumors (odds ratio [95%CI]: 0.46 [0.31‐0.90]). These findings indicate that mCRPC patients have a lower risk of experiencing severe neutropenia, possibly attributable to lower systemic exposure to docetaxel. [ABSTRACT FROM AUTHOR]